Aldehyde Dehydrogenase 1 Expression Research Articles

Immunohistochemical expression of putative cancer stem cell markers aldehyde dehydrogenase 1, SOX2, CD44 and OCT4 in different grades of oral epithelial dysplasia.

The hypothesized existence of cancer stem cells (CSC) and its markers aldehyde dehydrogenase 1 (ALDH1), CD44, SOX2 and OCT4 in oral dysplastic tissues provides the potential for a more reliable assessment of malignant transformation of oral epithelial dysplasia (OED). Thus, the present study is intended to evaluate the immunohistochemical expression of four different CSC markers ALDH1, CD44, SOX2 and OCT4 in different grades of OED and to investigate the co-expression of these putative stem cell markers in OED. A total of 35 samples of varying grades of OED which included 7 mild, 11 moderate and 17 severe dysplasia samples and 10 samples of normal oral mucosa without dysplasia were used. Four sections each from all 45 samples were stained with ALDH1, CD44, SOX2 and OCT4, respectively, by immunohistochemistry. The acquired data were analyzed and evaluated using the Chi-square test and unpaired t-test and the P < 0.05 was taken significant. ALDH1 and SOX2 expression percentages showed statistically significant differences among study groups (P < 0.05). Statistical comparison of percentage expression of CD44 and OCT4 between OED and normal was nonsignificant (P > 0.05). Co-expression of all four markers was found in 15 cases of OED with none of the normal cases showing co-expression. The expression of CSC markers in OED and normal mucosa differs significantly with co-expression of all four markers located only in dysplastic tissues. Until now, no single protein marker has been able to unequivocally identify the CSCs. Thus, a panel of putative CSC markers will help in identifying the patients with high risk for malignant transformation in OED.

Immunohistochemical comparative analysis of tumor stem cell biomarkers in pleomorphic adenoma, adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands

This study aimed to compare the immunoexpression profile of tumor stem cell (TSC) biomarkers CD44, aldehyde dehydrogenase 1 (ALDH1), OCT4, and SOX2 in salivary gland tumors (SGTs). Sixty tissue specimens of SGTs, including 20 pleomorphic adenomas, 20 adenoid cystic carcinomas (ACCs), and 20 mucoepidermoid carcinomas, in addition to 4 samples of normal glandular tissue, were subjected to immunohistochemistry. The expression of the biomarkers in the parenchyma and stroma was evaluated. Data were analyzed statistically by nonparametric tests (P < .05). Higher parenchymal expression of ALDH1, OCT4, and SOX2 was observed in pleomorphic adenomas, ACCs, and mucoepidermoid carcinomas, respectively. Most ACCs did not express ALDH1. Higher immunoexpression of ALDH1 in major SGTs (P = .021) and of OCT4 in minor SGTs (P = .011) was found. Immunoexpression of SOX2 was related to lesions without myoepithelial differentiation (P < .001) and malignant behavior (P = .002). Furthermore, OCT4 was related to myoepithelial differentiation (P = .009). CD44 expression was related to a better prognosis. Stromal immunoexpressions of CD44, ALDH1, and OCT4 were higher in malignant SGTs. Our findings suggest the participation of TSCs in the pathogenesis of SGTs. We emphasize the need for further investigations into the presence and role of TSCs in the stroma of these lesions.

Aldehyde dehydrogenase 1 expression in invasive breast carcinoma and its correlation with other clinicopathological parameters

Background Breast cancer is the main reason for mortality due to cancer among women worldwide. Activity of aldehyde dehydrogenase 1 (ALDH1) is known worldwide as a signature of breast malignancy stem cells. In this research, we tried to discover the variable expression of ALDH1 in diverse molecular categories of invasive breast duct carcinoma and its relation to other clinical and pathological parameters and to patient outcomes. Study design This is a retrospective study carried out on 118 samples of invasive breast duct carcinoma retrieved from the archives of Pathology Laboratory Department of Oncology Center, Mansoura University, Egypt. Patients and methods Immunostaining for ALDH1was done in addition to ER, PR, Her2, Ki67, EGFR, and CK5/6. Results We found that ALDH1 overexpression was found in 89% of cases. ALDH1 overexpression was considerably related to increased TNM staging (P=0.001). Moreover, disease-free survival was lesser in patients with ALDH1 overexpression than in patients with low ALDH1 expression. Conclusions Elevated ALDH1 expression is associated with aggressive traits as well as advanced TNM stage of breast cancer. Importantly, these discoveries may pave the way for novel cancer therapeutics based on ALDH1 inhibitors or antibodies.

Abstract P4-07-24: High Mammographic Breast density was correlated with overall survival of operable breast cancer which expressed CD44+CD24-/ALDH-1+

Abstract Background: Mammographic Breast Density (MBD) was known as a risk of breast cancer in either pre or postmenopausal women. The underlined mechanism remain unclear. Aldehyde dehydrogenase 1 (ALDH-1) and CD44+CD24− are the most consistently used biomarkers to identify and characterize breast cancer stem cells (CSCs). However, correlation between expression of CSCs and MBD remains unclear. We aimed to clarify the association between CD44, CD24 or ALDH-1 and the clinical factors including MBD for investigating their effects on overall survival (OS). Method: 159 operable breast cancers were finally included for double immune-histochemical staining of CD44, CD24 and single expression of ALDH-1. MBD was categorized according to the American College of Radiology Breast Imaging Reporting and Data System. Positive expression of CSC was defined when both Aldehyde dehydrogenase 1 (ALDH-1) and CD44+CD24− were expressed. Clinical values were age, co-morbidity (hypertension, hyperlipidemia, Diabetes Mellitus), body mass index, menopausal status. We also examined overall survival (OS) with the log-rank test. Result: Positive expression of BCSC was 33.3% (53/159 patients). It correlated with premenopausal status, high histologic grade, high Ki-67 expression, and low expression of ER or PR (Table 1). During mean 74 months, High BMD was correlated with worse OS in either pre- or postmenopausal patients (p=0.04) and worse OS in patients with co-morbidity (p=0.08). Expression of CSC was not associated with overall survival. In a group with CSC expression, patients of higher MBD(≥ 51%) was worse OS (p=0.046) compared with a group with non-CSC expression. Co-morbidity was significantly correlated with poor DFS in non-expressed group compared with CSC expressed group (p=0.01). In Cox-regression analysis, co-morbidity (HR=0.05, 95% CI: 0.006-0.44, p=0.007) and MBD ( HR= 0.14, 95% CI: 0.02-1.16, p=0.06) increased risk of OS. Conclusion: High MBD could be a prognostic factor in operable breast cancer. Each risk factor of survival was important, but host factors including comorbidity and MBD might be considered. Table 1.The correlation between BCSC and clinical variables in patient with operable breast cancerCSC(-)CSC(+)Number(%)Number(%)BMINormal68(65.4)36(34.6)0.63Obesity38(69.1)17(30.9)ComorbidityNo57(62.6)34(37.4)0.21Yes49(72.1)19(27.9)MBD≤ 50 %28(77.8)8(22.2)0.13≥ 51 %60(63.8)34(36.2)Age( year)&amp;lt;5040(63.5)23(36.5)0.49≥5066(68.8)30(31.3)MenopausePremenopause46(59.0)32(41.0)0.04Postmenopause60(74.1)21(25.9)HGGrade=116(80.0)4(20.0)0.02Grade=247(75.8)15(24.2)Grade=343(56.6)33(43.4)LVINo73(68.6)33(31.4)0.69Yes33(64.7)18(35.3)ERNegative42(52.5)38(47.5)&amp;lt;0.001Positive64(81.0)15(19.0)PRNegative65(61.3)41(38.7)0.043Positive41(77.4)12(22.6)Her-2/neunot expressed76(63.3)44(36.7)0.14overexpressed29(76.3)9(23.7)Ki-67negative68(80.0)17(20.0)&amp;lt;0.001positive38(51.4)26(48.6) Citation Format: JungSun Lee, Woo-Gyeong Kim. High Mammographic Breast density was correlated with overall survival of operable breast cancer which expressed CD44+CD24-/ALDH-1+ [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-24.

Association of ALDH1 with Response to Radiotherapy and Its Impact on Survival in Patients with Advanced Stage of Head and Neck Squamous Cell Carcinoma (HNSCC).

Background:The presence of cancer stem-like cells within tumor microenvironment distinctly governs response to chemo-radiotherapy. The ALDH1 (Aldehyde dehydrogenase 1) has emerged as a cancer stem cell (CSC) marker in various tumors. The aim of the study was to examine the expression of ALDH1 in HNSCC patients undergoing radiotherapy to evaluate its correlation with clinicopathological parameter, treatment response and survival. Methods:Expression of ALDH1 was evaluated by immunohistochemistry in 90 histopathologically confirmed HNSCC patients and 90 matched controls. The association between ALDH1 expression, clinicopathological parameters and treatment response was determined. Results:The immunohistochemistry results showed that ALDH1 was consistently expressed in all the HNSCC specimens although at different intensities. On the other hand, control specimens did not show similar expression of ALDH1. ALDH1 expression demonstrated statistically significant association with tumor size (p<0.001), lymph node status (p<0.001), stage (p<0.001), grade (p<0.001) and treatment response (p<0.001). Multivariate ordinal logistic regression analysis indicated alcohol and ALDH1 as an independent predictor of responsiveness to radiotherapy in HNSCC patients. Multivariate Cox regression analysis indicated that lymph node status (p=0.020), grade (p=0.006) and recurrence (p=0.002) were potential independent predictors of overall survival. Conclusion:From previous studies, ALDH1 has been contemplated not only as a promising prognostic and diagnostic marker but also as a likely drug target. Our study gives new understanding regarding the association between ALDH1, cancer prognosis and radioresistance. Our findings suggest that ALDH1, lymph node status, grade and alcohol could be the viable targets for HNSCC and it also provides new prospects for radiotherapy sensitivity in HNSCC.

ALDH1 expression and potential clinical implications in chronic inflammatory periapical lesions.

Aldehyde dehydrogenase 1 (ALDH-1) is a marker of stem cells in a variety of diseases, but its role in individuals with chronic inflammatory periapical lesions remains unknown. The aim of this study was to investigate the presence of cells with a stem cell profile based on the immunoexpression of ALDH-1 in periapical granulomas (PGs) and radicular cysts (RCs). A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to immunohistochemical study. The anti-ALDH-1 antibody was applied using the immunoperoxidase technique. An immunoexpression score (intensity vs. percentage of cells) was used, with the cases being classified as low expression (score: 0 to 4) and high expression (score: 6 to 9). The Chi-square test was used with a 5% level of significance. Immunoexpression of ALDH-1 was detected in all cases of PGs and RCs. In PG cases, the expression was diffuse in connective tissue cells, with most cases exhibiting high expression (n = 18; 69.2%), while in RC cases the expression revealed focal distribution in cells of the capsule and epithelial cells of the cystic lining, with most cases classified as low expression (n = 18; 72%). Significant differences in the expression scores of ALDH-1 were observed in PGs (p = 0.003). The variable expression of ALDH-1 suggests the presence of cells with stem cell profiles in PGs and RCs. These findings suggest that periapical tissues infiltrated by chronic inflammation can recruit important cells for the repair or evolution of periapical lesions.

Human Papilloma Virus and Cancer Stem Cell markers in Oral Epithelial Dysplasia-An Immunohistochemical Study.

ObjectivesTo study the correlation between the putative cancer stem cell (CSC) markers aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 44 (CD44), sex-determining region Y-box 2 (SOX2), and octamer-binding protein 4 (OCT4) and human papilloma virus (HPV) infection using p16, the surrogate marker of HPV in oral epithelial dysplasia (OED) and normal mucosa.MethodsFive sections each from 40 histopathologically diagnosed cases of different grades of OED and 10 cases of normal oral mucosa without dysplasia were immunohistochemically stained with p16, ALDH1, CD44, SOX2, and OCT4, respectively.ResultsExpression of ALDH1 and SOX2 was significantly increased in OED cases, whereas CD44 and OCT4 expression was increased in normal mucosa. P16-positive OED cases showed upregulation of ALDH1 and OCT4 expression as compared to p16-negative cases, while CD44 and SOX2 expression was downregulated in p16-positive OED cases; however, the results were not statistically significant.ConclusionThe present study indicated a suggestive link between p16 and cancer stem cell marker expression in HPV-associated OED, and that p16 has a significant role in CSC progression in OED. This is the first study to evaluate the expression of putative CSC markers in HPV-associated OED. However, low study numbers are a potential limiting factor in this study.

Epithelial membrane protein 3 regulates lung cancer stem cells via the TGF‑β signaling pathway.

Epithelial membrane protein 3 (EMP3) is a transmembrane glycoprotein that contains a peripheral myelin protein22 domain. EMP3 first received attention as a tumor suppressor, but accumulating evidence has since suggested that it may exhibit a tumor‑promoting function. Nonetheless, the biological function of EMP3 remains largely unclear with regards to its role in cancer. Herein, it was shown that EMP3 expression is upregulated in non‑small cell lung cancer (NSCLC) cells overexpressing aldehyde dehydrogenase1(ALDH1). EMP3 was shown to be involved in cell proliferation, the formation of cancer stem cells (CSCs) and in epithelial‑mesenchymal transition (EMT). The ability to resist irradiation, one of the characteristics of CSCs, decreased when the EMP3 mRNA expression was knocked down using small interfering RNA. In addition, when EMP3 knockdown reduced the migratory ability of cells, a characteristic of EMT. Additionally, it was shown that the TGF‑β/Smad signaling axis was a target of EMP3. EMP3 was found to interact with TGF‑β receptor type2 (TGFBR2) upon TGF‑β stimulation in lung CSCs (LCSC). As a result, binding of EMP3‑TGFBR2 regulates TGF‑β/Smad signaling activation and consequently affects CSCs and EMT. Kaplan‑Meier analysis results confirmed that patients with high expression of EMP3 had poor survival rates. Taken together, these findings showed that EMP3 may be a potential target for management of LCSCs with high expression of ALDH1, and that EMP3 is involved in TGF‑β/Smad signaling activation where it promotes acquisition of cancerous properties in tumors.

ALDH1 & CD133 in invasive cervical carcinoma & their association with the outcome of chemoradiation therapy.

Background & objectives:Chemoradiation is the standard therapy for locally advanced invasive cervical cancer and response to treatment determines the outcome. Cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT) play a role in response to treatment and hence the aim of this study was to evaluate if their levels in pre-treatment biopsies by immunohistochemistry (IHC) could predict response to treatment and outcome.Methods:The study comprised 60 patients with FIGO Stage IIB/III invasive cervical carcinoma treated by chemoradiation. They were divided into two groups based on their clinical outcome: group 1, 30 patients who had no evidence of disease at 48 month follow up and group 2, 30 patients who had disease relapse within 6-12 months of treatment completion. IHC was performed for CSC markers (ALDH1, CD133, Nanog and Oct-4), EMT markers (E-cadherin and vimentin) and squamocolumnar junction (KRT7) markers and H-scores determined. Intergroup comparison was performed. The expression of these markers was also evaluated in histological sections of cervical pre-cancer (CIN1 and CIN3) in comparison to normal cervix.Results:Cervical Intraepithelial Neoplasia grade 3 (CIN3) showed high expression of ALDH1 and KRT7 as compared to normal cervical epithelium. Aldehyde dehydrogenase 1 (ALDH1) and CD133 were overexpressed in 70 and 24 per cent cervical carcinoma cases whereas E-cadherin showed reduced expression in invasive carcinoma as compared to normal controls. ALDH1 overexpression was significantly associated with disease relapse in invasive cervical carcinoma treated by chemoradiation (P<0.01).Interpretation & conclusions:Determination of ALDH1 levels in pre-treatment cervical biopsies of invasive cervical carcinoma may be useful for prediction of response to chemoradiation, with high levels predicting for a poor response.

ALDH1 expression predicts progression of premalignant lesions to cancer in Type I endometrial carcinomas

In type 1 endometrial cancer, unopposed estrogen stimulation is thought to lead to endometrial hyperplasia which precedes malignant progression. Recent data from our group and others suggest that ALDH activity mediates stemness in endometrial cancer, but while aldehyde dehydrogenase 1 (ALDH1) has been suggested as a putative cancer stem cell marker in several cancer types, its clinical and prognostic value in endometrial cancer remains debated. The aim of this study was to investigate the clinical value of ALDH1 expression in endometrial hyperplasia and to determine its ability to predict progression to endometrial cancer. Interrogation of the TCGA database revealed upregulation of several isoforms in endometrial cancer, of which the ALDH1 isoforms collectively constituted the largest group. To translate its expression, a tissue microarray was previously constructed which contained a wide sampling of benign and malignant endometrial samples. The array contained a metachronous cohort of samples from individuals who either developed or did not develop endometrial cancer. Immunohistochemical staining was used to determine the intensity and frequency of ALDH1 expression. While benign proliferative and secretory endometrium showed very low levels of ALDH1, slightly higher expression was observed within the stratum basalis. In disease progression, cytoplasmic ALDH1 expression showed a step-wise increase between endometrial hyperplasia, atypical hyperplasia, and endometrial cancer. ALDH1 was also shown to be an early predictor of EC development, suggesting that it can serve as an independent prognostic indicator of patients with endometrial hyperplasia with or without atypia who would progress to cancer (p = 0.012).

Human Skeletal Muscle Satellite Cells Co-Express Aldehyde Dehydrogenase Isoforms Aldh1A1 andamp; Aldh1A3

Satellite cells (SC) constitute the stem cell population of skeletal muscle and conduct myogenic growth and differentiation. Recently, aldehyde dehydrogenase 1 (ALDH1) has been identified as a novel myogenic factor in experimental models of SCs. ALDH1 constitutes a subfamily of the ALDH enzyme super family. The enzymatic functions of ALDH1 isoforms include both protection against oxidative stress products and regulation of differentiation as pacemaker enzyme in retinoic acid signaling. Although ALDH enzymatic activity has been demonstrated in SCs it is not clear which isoforms are important in human skeletal muscle. Here, we show that ALDH1A1 and ALDH1A3 are expressed in human SCs. Using antibodies directed against ALDH1 and its isoforms ALDH1A1 and ALDH1A3, respectively, we demonstrate immunohistochemical staining in peri-fascicular position matching the localization of SCs. Consistently, co-immunofluorescence reveals ALDH1 expression in CD56 positive stem cells and co-localization of the isoforms ALDH1A1 and ALDH1A3 in Pax7 positive SCs. Quantitative analysis of immunohistochemical staining showed no significant differences in the distribution of ALDH1 positive SCs in the skeletal muscle groups pectoralis, diaphragm and psoas that have been investigated in the present study. In conclusion, human SCs co-express the ALDH1 isoforms ALDH1A1 and ALDH1A3.

Comparative analysis of aldehyde dehydrogenase 1 expression in polyps and adenocarcinoma of the distal colon

Aldehyde dehydrogenase 1 (ALDH1) is one of the most widely used cancer stem cells markers, even though the question of its significance for certain stages of colorectal carcinogenesis is still unclear. The aim of this study was to compare ALDH1 immunohistochemical expression levels in polyps and adenocarcinoma of the distal colon. Histopathological and immunohistochemical studies of biopsies from 40 patients (biopsies of polyps and histologically non-changed mucosa of the distal colon), as well as surgical material of colorectal adenocarcinoma from 30 patients were carried out. It was established that distal colonic polyps are characterized by cytoplasmic expression of ALDH1 with the median of relative area that is equal to 25.63 (18.26; 30.42)% stromal cells. ALDH1 expression by epitheliocytes is revealed exclusively in dysplastic polyps with the median of the area that is equal to 22.13 (17.22; 30.05)%. Colorectal adenocarcinoma is characterized by cytoplasmic expression of ALDH1 with the medians of the area that are equal to 40,22 (22,54; 47,77)% stromal cells and 32,12 (23.64; 40.28)% cancer cells. The area of ALDH1+ cells varies depending on the pTNM stage of the carcinoma, herewith the median of ALDH1+ stromal cells is significantly increasing during the tumor progression from the I to the III stages that displays increasing in number of stromal cells which are involved in oncogenic signaling pathways activation. The median of ALDH1+ cancer cells is significantly increasing during the tumor progression from the III to the IV stages that shows increasing number of cancer cells that acquire properties of stem cells on advanced stages of colorectal adenocarcinoma. Comparative analysis of the parameters obtained for polyps and carcinoma indicates that the median of ALDH1+ stromal cells area in polyps is 2 times smaller than the median of ALDH1+ stromal cells area in carcinoma, and the median of ALDH1+ epitheliocytes area in polyps is 1.5 times smaller than the median of ALDH1+ cancer cells area.

Aldehyde Dehydrogenase 1-related Genes in Triple-negative Breast Cancer Investigated Using Network Analysis.

Aldehyde dehydrogenase 1 (ALDH1) is known as a breast cancer stem cell (CSC) marker. This study aimed to identify genes associated with ALDH1. ALDH1-positive and -negative breast cancer cells were isolated using laser capture microdissection from five tissue samples of ALDH1-positive breast cancer patients. Messenger RNA expression levels were compared between ALDH1-positive and -negative cells. We found 104 differentially expressed genes between ALDH1-positive and -negative cells. Gene ontology and pathway analysis revealed that these genes were correlated with CSC functions and pathways. Network analyses identified 10 genes that were closely associated with ALDH1. We validated these 10 genes utilizing The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium cohort, and found that they were associated with ALDH1 expression and correlated with Wnt pathway signaling. The 10 genes we identified could be potential targets for CSC therapy of breast cancer.

Increased expression of ALDH-1 is associated with clinical parameters of salivary glands neoplasms

The enzyme aldehyde dehydrogenase-1 (ALDH-1) is a known putative tumour stem cells (TSC) marker, and these cells are implicated in carcinogenesis and progression of human neoplasms. We aimed to evaluate ALDH-1 expression in benign and malignant salivary gland neoplasms and its clinicopathological and prognostic significance. Expression of ALDH-1 was investigated by immunohistochemistry and confirmed by Western Blot analysis in 154 salivary gland neoplasms (103 malignant and 51 benign neoplasms). The expression was identified in the parenchyma of malignant (n = 88; 85.6%) and benign (100%) neoplasms. Overall, expression in the parenchyma varied considerably and was not associated with clinical parameters in most malignant neoplasms, however, a high expression in mucoepidermoid carcinomas (MEC) was associated with advanced pathological TNM stage (p = 0.047). The presence of ALDH-1 in stromal cells of malignant neoplasms (n = 67; 65.0%) was associated with lymph node metastasis (p = 0.032), tumour recurrence (p = 0.006) and death (p = 0.013). Overall and disease-free survival in 5 and 10 years was lower in patients with diagnosis of adenoid cystic carcinoma, tumour recurrence, advanced staging, and presence of ALDH-1 in the stroma. When adjusted by multivariate analysis, advanced staging and stromal expression were independent prognostic factors affecting disease-free survival. Our findings provide evidence that cells characterized as TSC in the parenchyma and stroma are differentially present among the different types of neoplasms studied and may be related to tumourigenesis, biological behaviour and persistence capacity of malignant tumours of the salivary gland.

Expression pattern of ALDH1, E-cadherin, Vimentin and Twist in early and late onset sporadic colorectal cancer.

Aim: To evaluate the expression pattern of ALDH1 (aldehyde dehydrogenase 1), E-cadherin, Vimentin and Twist in early and late onset sporadic colorectal cancer (CRC) and to study association of their expression with the occurrence of CRC at a young age. Materials & methods: Immunohistochemistry of ALDH1, E-cadherin, Vimentin and Twist was performed on 103 pretreated CRC biopsy samples. Results: ALDH1 expression was found to have strong correlation with early onset CRC (p < 0.0001). Conclusion: High ALDH1 expression correlates with the early onset of CRC. ALDH1 over-expression correlates with poor overall survival in colon cancer.

HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription.

Studies have shown that cancer stem cells (CSCs) are involved in resistance and metastasis of cancer; thus, therapies targeting CSCs have been proposed. Here, we report that heat shock 70-kDa protein 1-like (HSPA1L) is partly involved in enhancing epithelial–mesenchymal transition (EMT) and CSC-like properties in non-small cell lung cancer (NSCLC) cells. Aldehyde dehydrogenase 1 (ALDH1) is considered a CSC marker in some lung cancers. Here, we analyzed transcriptional changes in genes between ALDH1high and ALDH1low cells sorted from A549 NSCLC cells and found that HSPA1L was highly expressed in ALDH1high cells. HSPA1L played two important roles in enhancing CSC-like properties. First, HSPA1L interacts directly with IGF1Rβ and integrin αV to form a triple complex that is involved in IGF1Rβ activation. HSPA1L/integrin αV complex-associated IGF1Rβ activation intensified the EMT-associated cancer stemness and γ-radiation resistance through its downstream AKT/NF-κB or AKT/GSK3β/β-catenin activation pathway. Secondly, HSPA1L was also present in the nucleus and could bind directly to the promoter region of β-catenin to function as a transcription activator of β-catenin, an important signaling protein characterizing CSCs by regulating ALDH1 expression. HSPA1L may be a novel potential target for cancer treatment because it both enhances IGF1Rβ activation and regulates γβ-catenin transcription, accumulating CSC-like properties.

Prognostic Value of PET/CT and ALDH1 in Pancreatic Cancer and Correlation of Standardized Uptake Values with Clinical Characteristics and Survival

Abstract Background: Pancreatic malignancy is a rapidly growing cause of death in the world. Its survival rate is months even if discovered early. Aim of Study: We evaluated the correlations between PET/SUVs (Standard Uptake Values), clinical characteristics and cancer stem-like cells named aldehyde dehydrogenase 1 (ALDH1) in pancreatic cancer. We evaluated the diagnostic performance of SUV and its correlation with overall survival. Patients and Methods: Thirty-nine patients with pancreatic cancer were evaluated by PET/CT. The expression of ALDH1 was detected immunohistochemically in their cancer speci-mens. Results of PET/SUV were correlated with clinic-pathological character, ALDH1 and overall survival. Results: PET/SUV was associated significantly with tumor size (p=0.027). No significant correlation with other clinical-pathological characteristics. PET/CT showed sensitivity= 81%, specificity=78% and accuracy=82%. PET/SUV reflected the expression level of ALDH1 with significant correlation (p=0.001). Patients with high SUV and high expression of ALDH1 had a worse median overall. Conclusion: PET-CT was a non-invasive imaging modality that helped in pancreatic cancer especially in doubtful tumors. PET/CT was helpful tool to detect lymph nodes invasion and distant metastasis. It was associated with the expression level of ALDH1. High SUV and high expression of ALDH1were significantly correlated with a worse clinical outcome. PET/SUV and Cancer stem cells may serve as significant prognostic factors in predicting outcomes in pancreatic cancer patients.

The clinical and prognostic impact of aldehyde dehydrogenase 1 in non-small cell lung cancer: a meta-analysis.

BackgroundAldehyde dehydrogenase 1 (ALDH1) has been identified as a cancer stem cell marker. However, the clinical role of ALDH1 in non-small cell lung cancer (NSCLC) remains conflicting. This study was conducted to investigate the correlation of ALDH1 with NSCLC patients’ clinicopathological characteristics and prognosis.MethodsThe electronic databases were searched for the available literature. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) or hazard ratios (HRs: multivariate Cox analysis) with 95% CIs were used to evaluate the impact of ALDH1 on NSCLC.ResultsFinal 13 eligible studies with 2,407 patients published between 2009 and 2019 were identified. ALDH1 expression was not correlated with age, gender, smoking behavior, clinical stage, histological grade, lymph node metastasis, and distal metastasis, but the results demonstrated a positive association of ALDH1 expression with recurrence (yes vs. no: OR =2.82, 95% CI, 1.17–6.80, P=0.021) and a negative association of ALDH1 expression with vascular invasion (positive vs. negative: OR =0.63, 95% CI, 0.41–0.98, P=0.04). ALDH1 expression was significantly lower in adenocarcinoma (AD) than in squamous cell carcinoma (SCC) (OR =0.39, 95% CI, 0.30–0.51, P<0.001). Multivariate Cox analysis showed that ALDH1 expression was not associated with overall survival (OS) and disease-free survival (DFS), but was correlated with improved disease-specific survival (DSS) (HR =0.47, 95% CI, 0.22–0.98, P=0.043).ConclusionsALDH1 expression may be an independent favorable prognostic marker for DSS in NSCLC.

Aldehyde dehydrogenase 1, a target of miR-222, is expressed at elevated levels in cervical cancer.

The aim of the present study was to investigate the expression of microRNA-222 (miR-222) and aldehyde dehydrogenase 1 (ALDH1) in tissues and peripheral blood of cervical cancer patients, and to elucidate their underlying mechanisms of action. Tumor tissues and tumor-adjacent tissues were obtained from 33 cervical cancer patients and peripheral blood was obtained from these patients and 28 healthy subjects. The expression of miR-222 and ALDH1 mRNA was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To examine the levels of ALDH1 protein in tissues and blood, western blotting and ELISA were used. To confirm a direct interaction between miR-222 and ALDH1 mRNA, a dual luciferase reporter assay was performed. HeLA cells were transfected with agomiR-222 and expression of ALDH1 in the cells was measured by RT-qPCR and western blotting. MTT assay was preform to investigate the proliferation of HeLA cells. Expression of ALDH1 mRNA and protein was elevated in cervical cancer tissues and peripheral blood from patients compared with tumor-adjacent tissues and healthy controls, while the expression of miR-222 was reduced. Upregulation of miR-222 inhibited HeLA cell proliferation possibly due to a reduction in the expression of ALDH1. A dual luciferase reporter assay showed that miR-222 can bind with the 3′-untranslated seed region of ALDH1 mRNA to regulate its expression. miR-222 regulation of ALDH1 expression may play a role in the prevention of cervical cancer.

Overexpression of ALDH1 and EMT marker profile are linked with unfavorable outcome in head and neck cancer.

Background The aim of this research was to assess the expression of aldehyde dehydrogenase 1 (ALDH1) and epithelial-mesenchymal transition (EMT) markers in head and neck squamous cell carcinoma (HNSCC), and to correlate them with the clinical and histopathological parameters of a patient cohort with follow-up over an 8-year period. Material and Methods For this, seventeen HNSCC and non-neoplastic adjacent epithelium (AE) samples were subjected to laser microdissection and real-time PCR to evaluate the mRNA expression of ALDH1, E-cadherin (E-CAD), N-cadherin (N-CAD), and vimentin (VIM). Also, immunohistochemistry was performed for ALDH1, E-CAD, N-CAD, and VIM in the tumor center (TC), invasion front (IF), and AE of the seventeen samples. Mann-Whitney, Kruskal-Wallis and Chi-square tests were used to correlate the mRNA and immunohistochemical expression with different variables, considering p<0.05. Kaplan-Meier curves were produced for local recurrence, regional metastasis and treatment. Results A mRNA overexpression of ALDH1 in primary tumors was associated with regional metastasis and a high ALDH1 immunostaining was related to metastasis and a worse patient outcome. Additionally, a favorable outcome was associated with the transition phase and an unfavorable outcome was associated with EMT event. An overall 26.9 months was observed with longer survival associated with surgery and radiotherapy. Conclusions However, due to the intense variability inherent to the indicator proteins in the EMT process, the complete profile markers related to this biological process should be continuous investigated. Key words:Aldehyde dehydrogenase 1, epithelial mesenchymal transition, head and neck cancer, squamous cell carcinoma, follow-up study.